Tuberous sclerosis complex: clinical features, diagnosis, and prevalence within Northern Ireland

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes on chromosomes 9 and 16 respectively. Diagnosis is based on clinical features but can be difficult as a result of variable phenotypic expression. With the advantage of mutation analysis in making a diagnosis of TSC, and improved identification of the associated clinical features, there have been few new data on its prevalence and on the proportion of cases due to new mutations. We have performed a retrospective epidemiological study on the prevalence of TSC, the clinical features attributed to it, and the availability of mutational analysis. We identified 73 known patients with TSC (5 deceased): 39 were female and 34 male. Ages ranged from 10 months to 69 years, with a mean age of 27 years 11 months (SD 16y 10mo). The point prevalence of TSC in our study was estimated at I out of 24 956 on the prevalence day (30 April 2004). The majority of patients (42.5%) were diagnosed at less than 15 months of age; 25% were not given a diagnosis on first developing symptoms. In all, 93.2% had epilepsy and 71.2% had a learning disability.* A mutation was identified in 95.8% of those tested (26% TSC1 and 74% TSC2). TSC2 mutations were correlated with a more severe phenotype. The new mutation rate was calculated at 64%. We conclude that the prevalence of TSC is higher than previously calculated. We recommend that all children with epilepsy be assessed for features of TSC. Larger studies will be required to assess the prevalence of mutations in each gene, and genotype-phenotype correlation.

Trisomy 10p with clinical features of facio-auriculo-vertebral spectrum: a case report

We report a male child born with complete absence of his external ear, hemifacial microsomia of the right side, high arched palate, a down-turned upper lip and slightly upslanting palpebral fissures. The features were suggestive of facio-auriculo-vertebral spectrum. Investigations showed a tandem duplication of the short arm of one chromosome 10 with apparent breakpoints at p14 and p15. This case extends the list of chromosomal abnormalities associated with the facio-auriculo-vertebral phenotype and also adds useful clinical information to possible trisomy 10p phenotypes.

Mosaic monosomy 14: clinical features and recognizable facies

A 1-year-old child with clinical features of monosomy 14 is reported. She has dysmorphic facial features including ocular colobomata, dolichocephaly and microcephaly, retinal pigmentation, severe seizures, fair curly hair and tapering fingers. There was severe mental retardation. This is the first reported case of severe mosaic monosomy 14, with up to 30% mosaicism. A recognizable facial gestalt is present in children with 14q deletions or partial monosomy 14, as well as susceptibility to infection, feeding difficulties, seizures and retinal pigmentation. (C) 2004 Lippincott Williams Wilkins.

Polymorphisms in SLC6A4, PAH, GABRB3, and MAOB and modification of psychotic disorder features

We tested four genes [phenylalanine hydroxylase (PAH), the serotonin transporter (SLC6A4), monoamine oxidase B (MAOB), and the gamma-aminobutyric acid A receptor beta-3 subunit (GABRB3)] for their impact on five schizophrenia symptom factors: delusions, hallucinations, mania, depression, and negative symptoms. In a 90 family subset of the Irish Study of High Density Schizophrenia Families, the PAH 232 bp microsatellite allele demonstrated significant association with the delusions factor using both QTDT (F = 8.0, p = .031) and QPDTPHASE (chi-square = 12.54, p = .028). Also, a significant association between the GABRB3 191 bp allele and the hallucinations factor was detected using QPDTPHASE (chi-square 15.51, p = .030), but not QTDT (chi-square = 2.07, p = .560). (C) 2009 Elsevier B.V. All rights reserved.

Are there clinical features of a sensitized cough reflex?

Cough reflex hypersensitization is a key feature in patients with troublesome cough. The clinical consequence of this hypersensitive state is typified by bouts of coughing often triggered by low threshold stimuli encountered by the patient during normal daily activities including exposure to aerosols, scents and odours, a change in air temperature and when talking or laughing. These features are often perceived by cough patients to be the most disruptive aspect of their condition and undoubtedly contribute to impaired quality of life. Patients with troublesome cough may describe a range of additional symptoms and sensations including an 'urge to cough' or the feeling of an 'itch' at the back of the throat, or a choking sensation and occasionally chest pain or breathlessness. It is uncertain if these features arise due to the processes responsible for cough reflex sensitization or as a direct consequence of the underlying cough aetiology. In an attempt to understand the clinical features of a sensitized cough reflex, the spectrum of symptoms typically described by cough patients will be reviewed and possible underlying mechanisms considered. Since an intact cough reflex is crucial to airway protection, anti-tussive treatment that attenuates the hypersensitive cough state rather than abolishing the cough reflex completely would be preferable. Identifying such agents remains a clinical, scientific and pharmacological challenge. (c) 2008 Elsevier Ltd. All rights reserved.

Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations

Although approximately 95% of patients with polycythemia vera (PV) harbor the V617F mutation in JAK2 exon 14, several mutations in exon 12 have been described in the remaining patients. We conducted a European collaborative study to define the molecular and clinical features of patients harboring these mutations. Overall, 106 PVs were recruited and 17 different mutations identified. Irrespective of the mutation, two-thirds of patients had isolated erythrocytosis, whereas the remaining subjects had erythrocytosis plus leukocytosis and/or thrombocytosis. Compared with JAK2 (V617F)-positive PV patients, those with exon 12 mutations had significantly higher hemoglobin level and lower platelet and leukocyte counts at diagnosis but similar incidences of thrombosis, myelofibrosis, leukemia, and death. In a multivariable analysis, age more than 60 years and prior thrombosis predicted thrombosis. These findings suggest that, despite the phenotypical difference, the outcome of JAK2 exon 12 mutations-positive PV is similar to that of JAK2 (V617F)positive PV. (Blood. 2011; 117(10):2813-2816)

High-velocity features: A ubiquitous property of Type Ia supernovae

Evidence of high-velocity features (HVFs) such as those seen in the near-maximum spectra of some Type Ia supernovae (SNe Ia; e. g., SN 2000cx) has been searched for in the available SN Ia spectra observed earlier than 1 week before B maximum. Recent observational efforts have doubled the number of SNe Ia with very early spectra. Remarkably, all SNe Ia with early data ( seven in our Research Training Network sample and 10 from other programs) show signs of such features, to a greater or lesser degree, in Ca II IR and some also in the Si II lambda 6355 line. HVFs may be interpreted as abundance or density enhancements. Abundance enhancements would imply an outer region dominated by Si and Ca. Density enhancements may result from the sweeping up of circumstellar material (CSM) by the highest velocity SN ejecta. In this scenario, the high incidence of HVFs suggests that a thick disk and/or a high-density companion wind surrounds the exploding white dwarf, as may be the case in single degenerate systems. Large-scale angular fluctuations in the radial density and abundance distribution may also be responsible: this could originate in the explosion and would suggest a deflagration as the more likely explosion mechanism. CSM interaction and surface fluctuations may coexist, possibly leaving different signatures on the spectrum. In some SNe, the HVFs are narrowly confined in velocity, suggesting the ejection of blobs of burned material.

Aerospace Stiffened Panel Initial Sizing With Novel Skin Sub-Stiffening Features

The introduction of skin sub-stiffening features has the potential to modify the local stability and fatigue crack growth performance of stiffened panels. Proposed herein is a method to enable initial static strength sizing of panels with such skin sub-stiffening features. The method uses bespoke skin buckling coefficients, automatically generated by Finite Element analysis and thus limits the modification to the conventional aerospace panel initial sizing process. The approach is demonstrated herein and validated for prismatic sub-stiffening features. Moreover, examination of the generated buckling coefficient data illustrates the influence of skin sub-stiffening on buckling behavior, with static strength increases typically corresponding to a reduction in the number of initial skin longitudinal buckle half-waves.

A comparative analysis of multidimensional features of objects resembling sets of graphs

In the present paper, we introduce a notion of a style representing abstract, complex objects having characteristics that can be represented as structured objects. Furthermore, we provide some mathematical properties of such styles. As a main result, we present a novel approach to perform a meaningful comparative analysis of such styles by defining and using graph-theoretic measures. We compare two styles by comparing the underlying feature sets representing sets of graph structurally. To determine the structural similarity between the underlying graphs, we use graph similarity measures that are computationally efficient. More precisely, in order to compare styles, we map each feature set to a so-called median graph and compare the resulting median graphs. As an application, we perform an experimental study to compare special styles representing sets of undirected graphs and present numerical results thereof. (C) 2007 Elsevier Inc. All rights reserved.